This laboratory has in progress a study to characterize the proteins of the human lens. The lens consists of a few very high abundance proteins called the crystallins and several hundred lesser abundance proteins. During the life of the lens, the proteins become extensively modified. Methodologies have been developed to yield good separation of the proteins using two- dimensional polyacrylamide gel electrophoresis. Due to the extensive modifications, identification of the proteins is based on immunotechniques and sequencing. Normal donor lenses varying in age from fetal to 70 years and cataracts of different etiologies have been analyzed. The regions of t normal lenses are identified by structure patterns. The cortex has been separated into three different layers, and each of the developmentally defined nuclear regions has been separated. The protein patterns in each of the cortical regions are distinguishable as cortex with the characterist large protein spots corresponding to each of the major crystallins. The protein patterns of the nuclear regions are all similar to each other but clearly unique from those of the cortical regions. Protein spots corresponding to the major crystallins are not readily visible. Many new spots are present, including numerous low molecular weight spots that are fragments of crystallins. These results have significance in understanding the potential role of protein modification in cataractogenesis. The protei throughout the lens are being identified, yielding a database of informatio on the normal human lens. The protein patterns of numerous cataracts have been determined. These data are now being analyzed with respect to the cataract etiology.